Exiguolide is one of macrocyclic lactones isolated from sponges and is known to have an activity of inhibiting maturation of ova and spermatozoa of Hemicentrotus pulcherrimus (Non Patent Literature 1). Exiguolide has a 20-membered cyclic macrolide structure including a partial structure similar to bryostatins. Regarding chemical synthesis of exiguolide, total synthesis of (+)exiguolide has been published by a group of Seoul National University in 2008 (Non Patent Literature 2), and total synthesis of (−)exiguolide has been published by the present inventors in 2010 (Non Patent Literature 3).
Various macrolide compounds naturally exist, and macrolide compounds having various bioactivities, such as antibacterial agents, antifungal agents, and immunosuppressive agents, are known. Among these compounds, macrolide antibiotics are particularly useful. For example, erythromycin discovered from Streptomyces and its analogs such as clarithromycin are known.
It is also known that the macrolide compounds include many compounds showing anticancer activities through cytotoxicity or immune activity (Patent Literatures 1 to 7). Bryostatins are one example thereof. Bryostatins are natural macrolide compounds isolated from marine organisms, and not less than twenty analogs are known. At present, bryostatins are under many clinical tests for, for example, leukemia or Alzheimer dementia and are expected to show advantageous effects in combination with other anticancer drugs or effects of overcoming multiple drug resistance. The structure of exiguolides can be recognized as a simplified analog of the bryostatins (Non Patent Literature 4), and exiguolides are expected to have various bioactivities. However, any bioactivity, such as a cell growth-inhibiting activity or anticancer activity, has not been verified in the exiguolide.